Formate in serum and urine after controlled methanol exposure at the threshold limit value.

Abstract

Methanol will be present as a new air pollutant when methanol-powered vehicles are introduced in the United States. Little is known about the effect of low-dose methanol exposure. It is controversial whether or not formate, the main metabolite responsible for methanol's acute toxicity, is a sensitive biological marker of toxicity or exposure. We studied the effect of a 4-hr exposure at rest to 200 ppm of methanol vapors on endogenous serum formate and on urinary formic acid excretion. A randomized, double-blind study of human exposure to a constant concentration of methanol was performed in a whole-body exposure chamber. Twenty-six healthy volunteers, each serving as his or her own control, participated in sham and methanol exposures. Urine (at 0, 4, 8 hr) and serum specimens (15 time points over 8 hr) collected before, during, and after the exposure were measured for formate. We found no significant differences in serum formate concentration between exposure and control conditions either at any time point or for area under the curve. Mean concentrations at the end of the exposure were: exposed 14.28 +/- 8.90 mg/l and control 12.68 +/- 6.43 mg/l. A slight, but nonsignificant (p = 0.08), increase in urine formate excretion rate was found at 4 hr (exposed 2.17 +/- 1.69 mg/4 hr and control 1.67 +/- 1.02 mg/4 hr). Age, sex, folic acid level, and smoking were not significant covariates. At 200 ppm, methanol exposure does not contribute substantially to endogenous formate quantities. Serum and urine formate determinations are not sensitive biological markers of methanol exposure at the threshold limit value. Images p178-a

Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects

“…Clinical studies did not note serum toxic formaldehyde concentrations, which may ultimately lead to metabolic acidosis, loss of vision, and death [ 117 , 118 ]. Indeed, physiological or fospropofol infusion-related formate concentrations have been measured in the range of 13 ± 7 μ g/mL [ 119 ], while formate concentrations in patients who died of methanol intoxication were reported to be at least 350 times higher in the range of 7–11 mg/mL [ 120 ].…”

Evaluation of Fumaric Acid and Maleic Acid as Internal Standards for NMR Analysis of Protein Precipitated Plasma, Serum, and Whole Blood

“…For example, in a study using intact serum, formic acid has been evaluated as an alternative to TSP . However, endogenous formic acid, which varies significantly from person to person (∼40 to 350 μM), interferes with externally added formic acid, and hence, formic acid is unsuitable as a reference for quantitation. − In another study using intact rat plasma, DSA (4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate), which is a derivative of DSS, was evaluated as a potential internal standard . However, several factors, including its increased line broadening by a factor of >2 at pH 7.4 relative to pH 3.0, indicate its interaction with the sample matrix, and hence, it is also unsuitable as a reliable internal standard.…”

Final Report of the Cosmetic Ingredient Review Expert Panel on the Safety Assessment of Methyl Acetate

“…Human volunteers (n = 27; age 20-55 years) were exposed to 200 ppm methanol (the Occupational Safety and Health Administration [OSHA] Permissible Exposure Limit) for 4 hours and to water vapor for 4 hours in a double-blind, random study. 35 Urine samples were collected at 0, 4, and 8 hours and blood samples were collected from the participants before they entered the chamber, every 15 minutes for the first hour, every 30 minutes from the first to the third hour and at 4 hours. Urine and serum samples were analyzed for formate (LOD 0.5 mg/L).…”